Carboxyamidotriazole Orotate With Temozolomide May Be Active Against Glioblastoma
EGFR-amplified tumors had a high rate of response.
Carboxyamidotriazole orotate (CTO) plus temozolomide (TMZ) or chemoradiation may be safe and effective among patients with glioblastoma (GBM) or anaplastic glioma (AG), according to a study published in the Journal of Clinical Oncology.1
For this phase 1B study (ClinicalTrials.gov Identifier: NCT01107522), researchers enrolled 47 patients and assigned them to 1 of 2 cohorts. In cohort 1, patients with recurrent GBM/AG were treated with escalating CTO (219 to 812.5 mg/m2once daily or 600 mg fixed once-daily) plus TMZ; in cohort 2, patients newly diagnosed with GBM received escalating doses of CTO (219 to 481 mg/m2once daily) plus radiotherapy and TMZ.
CTO did not disrupt TMZ levels. Although toxicities were observed including fatigue, constipation, nausea, and hypophosphatemia, none were dose-limiting; the recommended phase 2 dose was 600 mg once daily.
In cohort 1, 1 and 6 patients had complete and partial responses, respectively.
In cohort 2, patients had a median progression-free survival of 15 months, and the median overall survival (OS) was not reached after a median follow-up of 28 months. The 2-year OS rate was 62%. EGFR-amplified tumors, furthermore, had a high rate of response (P= .005).
The authors concluded that “[o]n the basis of the favorable toxicity profile, brain penetration, and encouraging activity observed in this difficult-to-treat population of patients with GBM and AG, randomized phase II trials with CTO in combination with TMZ or chemoradiation are planned.”
- Omuro A, Beal K, McNeill K, et al. Multicenter phase IB trial of carboxyamidotriazole orotate and temozolomide for recurrent and newly diagnosed glioblastoma and other anaplastic gliomas. J Clin Oncol. 2018 Apr 23. doi: 10.1200/JCO.2017.76.9992 [Epub ahead of print]